S280: B-CELL MALIGNANCIES TREATED WITH TARGETED DRUGS AND SARS-COV-2 INFECTION. A EUROPEAN HEMATOLOGY ASSOCIATION SURVEY (EPICOVIDEHA)
Authors: M. S. Infante, J. Salmanton-García, A. Fernandez-Cruz, F. Marchesi, Z. RÁČIL, M. Hanakova, O. Jaksic, B. Weinbergerova, C. Besson, R. Duarte, F. Itri, T. VALKOVIĆ, A. Busca, A. Guidetti, A. GLENTHØJ, G. Collins, V. Bonuomo, U. Sili, G. Seval, M. Machado, A. Lopez-Garcia, R. Cordoba, O. Blennow, G. Abu-zeinah, S. Lemure, A. Kulasekararaj, I. Falces-Romero, C. Cattaneo, O. A. Cornely, J.-A. Hernandez-Rivas, L. Pagano
Journal: HemaSphere (2022)

Background: Patients with lymphoproliferative diseases (LPD) appear particularly vulnerable to SARS-CoV-2 infection, partly because of the effects of the anti-neoplastic regimens (chemotherapy, signaling pathway inhibitors, and monoclonal antibodies) on the immune system. The real impact of COVID-19 on the life expectancy of patients with different subtypes of lymphoma and targeted treatment is still unknown. Aims: The aim of this study is to describe and analyse the outcome of COVID-19 patients with underlying LPD treated with targeted drugs such as monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab or pembrolizumab), BTK inhibitors (ibrutinib, acalabrutinib), PI3K inhibitors (idelalisib), BCL2 inhibitors (venetoclax) and IMIDs, (lenalidomide). Methods: The survey was supported by EPICOVIDEHA registry. Adult patients with baseline CLL or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between January 2020 and January 2022 were selected. Results: The study included 368 patients (CLL n=205, 55.7%; NHL n=163, 44.3%) treated with targeted drugs (Table 1). Median follow-up was 70.5 days (range 19-159). Most used targeted drugs were ITKs (51.1%), anti-CD20 other than rituximab (16%), BCL2 inhibitors (7.3%) and lenalidomide (7.9%). Of note, only 16.0% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Pulmonary symptoms were present at diagnosis in 244 patients (66.2%). Severe COVID-19 was observed in 47.8 % patients while 21.7% were admitted to to intensive care unit (ICU), being 55 (26.8%) CLL patients and 25 (15.3%) NHL patients. More comorbidities were reported in patients with severe-critical COVID-19 compared to those with mild- asymptomatic infection (p=0.002). This difference was relevant in patients with chronic heart diseases (p=0.005). Overall, 134 patients (36.4%) died. Primary cause of death was COVID-19 in 92 patients (68.7%), LPD in 14 patients (10.4%), and a combination of both in 28 patients (20.9%).Mortality was 24.2% (89/368) at day 30 and 34.5%(127/368) at day 200. After a Cox multivariable regression age >75 years (p<0.001, HR 1.030), active malignancy (p=0.011, HR 1.574) and admission to ICU (p<0.00, HR 4.624) were observed as risk factors. Survival in patients admitted to ICU was 33.7% (LLC 38.1%, NHL 24%). Mortality rate decreased depending on vaccination status, being 34.2% in not vaccinated patients, 15.9-18% with one or two doses, decreasing to 9.7% in patients with booster dose (p<0.001). There was no difference in OS in NLH vs CLL patients (p=0.344), nor in ITKs vs no ITKs treated patients (p=0.987). Additionally, mortality rate dropped from the first semester 2020 (41.3%) to last semester 2021 (25%). Image:Summary/Conclusion: - Our results confirm that patients with B-malignancies treated with targeted drugs have a high risk of severe infection (47.8%) and mortality (36.4%) from COVID-19. - Presence of comorbidities, especially heart disease, is a risk factor for severe COVID-19 infection in our series. - Age >75 years, active malignancy at COVID-19 onset and ICU admission were mortality risk factors. - COVID-19 vaccination was a protective factor for mortality, even in this population with humoral immunity impairment. - The learning curve in the management of the infection throughout the pandemic and the development of COVID-19 treatments showed benefit in this particularly vulnerable population.